Pirenzepine--a ligand with original binding properties to muscarinic receptors.

Pirenzepine has been shown to evoke a variety of antimuscarinic effects in animals. However, in contrast to classical antimuscarinic drugs, pirenzepine inhibits gastric acid secretion at much lower doses than those required to block smooth muscle action and to cause tachycardia. To investigate this novel behaviour we have compared the binding properties of pirenzepine to muscarinic receptors with those of a classical muscarinic antagonist, N-methyl-scopolamine. Binding has been determined in subcellular preparations of the sublingual, submandibular, parotid and lacrimal glands, smooth muscle of ileum and stomach, heart and several brain regions of the rat. Whereas N-methyl-scopolamine binds to an apparently uniform population of muscarinic receptors with little regional variation in affinity constant, the binding of pirenzepine in peripheral tissues is characterised by its low affinity in smooth muscle and the heart and considerably higher affinities to muscarinic receptors in exocrine glands and fundus mucosa, in agreement with the pharmacological profile of the drug. Furthermore, within the central nervous system and some exocrine glands, pirenzepine distinguishes between subclasses of muscarinic receptors which are not detected by classical antagonists. This evidence suggests that the unusual receptor binding properties of pirenzepine may make its selective antimuscarinic action possible.